Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen. Moreover, grafted D2F2 tumor cells grew faster and intratumoral Foxp3+ cell accumulation was observed in these mice compared to sham-treated controls. Results from reporter cell lines suggested that acrolein acts via the aryl-hydrocarbon receptor which could be inhibited by resveratrol and 3'-methoxy-4'-nitroflavone Acrolein- stimulation of human PBMCs increased Foxp3+ expression by T cells which could be antagonized by resveratrol. Our mouse and human data thus revealed that acrolein exerts systemic immunosuppression by promoting Foxp3+ regulatory cells. This provides a novel explanation why smokers have a lower allergy, but higher cancer risk.
- MeSH
- akrolein farmakologie MeSH
- alergeny imunologie MeSH
- alergie imunologie prevence a kontrola MeSH
- cytokiny metabolismus MeSH
- forkhead transkripční faktory metabolismus MeSH
- imunologické faktory farmakologie MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádory imunologie metabolismus MeSH
- NF-kappa B metabolismus MeSH
- plíce imunologie metabolismus patologie MeSH
- receptory aromatických uhlovodíků metabolismus MeSH
- regulační T-lymfocyty imunologie metabolismus MeSH
- resveratrol MeSH
- signální transdukce MeSH
- stilbeny farmakologie MeSH
- tvorba protilátek imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
